The recent availability of highly active antiretroviral therapy (HAART) regimens, and in particular the class of HIV-1 protease inhibitors, has dramatically improved the outlook for many HIV-infected patients. However, HAART regimens often require multiple pills, strict dosing schedules, and certain dietary restrictions. Missed doses of protease inhibitors may lead to more rapid selection of drug-resistant viral strains and adversely impact all subsequent treatment decisions. Studies demonstrate that adherence to drug regimens is improved when all pills can be administered once or twice daily. Combining protease inhibitor compounds has the potential to provide potent antiretroviral effects in a simpler regimen (longer intervals, fewer pills). The current study is designed to explore the possibility of once-a-day dosing of HAAART based on pharmacokinetic interactions between soft gel saquinavir (sgcSAC) and ritonavir (RTV). Saquinavir (SAQ) was first developed as a hard gel capsule with good in vitro activity, but poor oral absorption. Ritonavir (RTV) is an inhibitor of both cytochrome p450 and HIV protease, increasing the levels of saquinavir in the blood to reach clinical efficacy. Soft gel capsule SAQ has excellent oral absorption, and has been shown to be as effective as HGC saquinavir with RTV. RTV may substantially increase sgcSAQ levels, avoiding multiple pills, doses, and possibly some adverse effects seen with RTV at higher doses. Sixty-four HIV-negative volunteers will be enrolled into a pharmacokinetic study lasting for 15 days. One group of 8 subjects will take a standard dose of sgcSAQ; 7 other groups will be randomized to varying combinations of sgcSAQ and RTV. Doses will be given with standardized meals, and pharmacokinetic data measured. Patients will undergo intensive inpatient monitoring for two days and 12 dayss of outpatient monitoring. Hopefully, the data gathered from this study will create a safe, simpler regimen for HIV patients. This study will be a pilot study for a later therapeutic study in HIV infected patients.